Process analytical technology (PAT), as defined by the United States Food and Drug Administration (FDA), is a mechanism to design, analyze, and control pharmaceutical manufacturing processes through the measurement of Critical Process Parameters (CPP) which affect Critical Quality Attributes (CQA). By defining the CPPs, and then being able to monitor them quickly and accurately (preferably in-line or on-line), pharmaceutical companies, among others, are able to benefit from more efficient testing methods that lead to more consistent and efficient processes, whilst at the same time reducing risk.
Index of Refraction (IoR) sensors are examples of PAT, and are starting to see increased use in some critical process applications, such as media and buffer preparation, chromatography and clean-in-place (CIP) operations among others. These process steps require accurate liquid chemical concentration and temperature monitoring, as any mistakes can be very costly. Systems for refractive index measurement of a sample utilize principles of physics underlying the measurement of critical angle to determine refractive index of a medium. When light traveling from a high index medium is incident upon an interface between the high index medium and another medium having a lower refractive index at angles of incidence larger than a critical angle of incidence, total internal reflection may be observed. The critical angle is a function of the refractive index of both media. However, if the refractive index of one medium is known, the refractive index of the other may be determined from a measurement of the critical angle θc using a well-known formula. This refractive index measurement can correlate with a concentration of a species within a sample.
In some cases these IoR sensors have been utilized in processes such as those in the biotechnology and biopharmaceutical manufacturing markets. These type of processes include upstream applications such as mixing, clarification, and sterilizing filtration and downstream applications including cell harvesting, clarification, chromatography concentration and diafiltration, contaminant removal, and buffer preparation.
It is thus desired to provide standalone (also referred to as bench-top) IoR sensor systems that will enable entities to develop the PAT parameters for critical steps of their processes at bench scale (lab), early in a development cycle (e.g., for drug development). This will allow such entities to leverage the utility of such IoR sensors in multiple settings and more easily integrate the IoR measurements (or associated concentration measurements) into their processes, including their production processes.